Conradi–Hünermann–Happle syndrome in males vs. MEND syndrome (male EBP disorder with neurological defects)

Summary Background  There is confusion in the literature concerning disorders caused by EBP (emopamil‐binding protein) mutations in males. Objectives  To study the clinical and genetic differences in males affected either with Conradi–Hünermann–Happle (CHH) syndrome (X‐linked dominant chondrodysplasia punctata, CDPX2) or with a nonmosaic, X‐linked recessive disorder for which we propose the acronymic term MEND syndrome ( m ale E BP disorder with n eurological d efects). Methods  We report a 7‐year‐old boy with a history of transient scaly erythematous lesions on his limbs, trunk and scalp soon after birth. DNA was isolated from ethylenediamine tetraacetic acid‐blood samples of the patient and the four coding exons of the EBP gene were amplified by polymerase chain reaction. We review all published cases of CHH syndrome in males in the literature and elaborate the clinical and genetic differences between CHH syndrome in males and MEND syndrome. Results  We found at position 33 of the EBP gene the variant c.33C>A leading to the same nonsense mutation p.Y11X that had previously occurred de novo in a female with typical manifestations of CHH syndrome. When the known male cases with EBP mutations were reviewed, a striking nosological difference between the mosaic and nonmosaic phenotypes was evident. Clear‐cut clinical criteria are elaborated to distinguish between CHH syndrome in males and MEND syndrome. Conclusions  Because the clinical outcome and prognosis are different it is important to distinguish between males with CHH syndrome that represents a mosaic phenotype, and those with MEND syndrome that is a nonmosaic trait.